Pharmaceutical Research

, Volume 27, Issue 7, pp 1309–1317 | Cite as

Multivariate Data Analysis of Factors Affecting the In Vitro Dissolution Rate and the Apparent Solubility for a Model Basic Drug Substance in Aqueous Media

  • Anita Maria Persson
  • Curt Pettersson
  • Josefin Rosén
Research Paper



To evaluate the usefulness of a miniaturized rotating disk equipment for the determination of factors influencing the in vitro dissolution rate, G, of a model basic drug substance (terfenadine) in different aqueous media, using experimental design and multivariate data analysis. The apparent solubility, S, was included in the chemometric study.


The dissolution rate was determined with a miniaturized rotating disk apparatus and the solubility by shake-flask methodology. Media were based on acetate, phosphate or maleate buffers—the latter used in fasted state simulated intestinal fluid (FaSSIF-V2). The chemometric analyses included fractional factorial design, principal component analysis (PCA) and orthogonal partial least squares (OPLS). Quantifications were made with a RP-HPLC-DAD system.


The most influential factor for both G and S of terfenadine in the different media was pH. Apart from the ionic strength and sodium chloride concentration in the acetate medium, the effects of the other variables were insignificant, implying no wetting effect of the surfactants.


The miniaturized rotating disk equipment was suitable to use, in conjunction with the chemometric analyses, in the evaluation of the factors affecting the in vitro dissolution rate. The apparent solubility was found to be influenced by the same factors as G.


chemometrics dissolution media dissolution rate miniaturized rotating disk equipment solubility 





biopharmaceutical classification system


critical micelle concentration


diode array detector


design of experiments


in vitro dissolution rate




ionic strength


in vitro/in vivo correlation


sodium chloride


sodium taurocholate


orthogonal partial least squares


principal component analysis


reversed phase high-performance liquid chromatography


relative standard deviation


apparent solubility


trifluoroacetic acid



The authors would like to thank Walter Lindberg, AstraZeneca Mölndal, Sweden, for letting us borrow the miniaturized rotating disk equipment. Anders Sokolowski, AS Consulting Uppsala, Sweden, is thanked for all the exceptional help in the media and buffer calculations/recipes used in this study. Expressed gratitude is made to Eva M. Karlsson, Anders S. Carlsson and Anders AS. Karlsson, AstraZeneca Mölndal, Sweden, for the generous donation of the surfactants (NaTC and lecithin). Johan Gottfries, Gottfries Medicinal AB Göteborg, Sweden, is thanked for all constructive discussions of the multivariate data analysis. Financial support from the Carl Trygger Foundation, Sweden, is gratefully acknowledged.

Supplementary material

11095_2010_111_MOESM1_ESM.doc (91 kb)
Supplementary Material 1 (DOC 91 kb)


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Anita Maria Persson
    • 1
  • Curt Pettersson
    • 1
  • Josefin Rosén
    • 2
  1. 1.Division of Analytical Pharmaceutical ChemistryUppsala UniversityUppsalaSweden
  2. 2.Divison of PharmacognosyUppsala UniversityUppsalaSweden

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